Department of Clinical pharmacy, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China.
Food Funct. 2019 Aug 1;10(8):5102-5114. doi: 10.1039/c9fo00957d. Epub 2019 Jul 31.
The present study was designed to investigate the protective effects of Cordyceps militaris polysaccharides (CMP) on STZ-treated DN mice. CMP were identified by FT-IR and HPLC. Diabetic nephropathy (DN) was induced in male C57BL/6 mice by the injection of streptozotocin (STZ, 50 mg kg) in citrate buffer on 5 consecutive days. Administration of CMP at 200 and 400 mg kg or irbesartan at 60 mg kg in the STZ-treated mice could prevent the damage caused by STZ. CMP significantly reduced the STZ-induced higher expression of the kidney index, TC, TG, MDA, urinary protein, Scr, and BUN, while it markedly increased the STZ-induced decrease in GSH levels compared with the DN group. Histopathology analysis of the kidney by PAS, Masson, and HE staining confirmed the renal injury induced by STZ and the protective effects of CMP. Transmission electron microscopy (TEM) results confirmed the severe foot process effacement induced by STZ, but CMP treatment inhibited the podocytes' structure defects and ameliorated the function of podocytes. Desmin was measured by immunofluorescence and was related to podocyte injury. The results showed that CMP lessened the expression of desmin induced by STZ. CD68 expression was measured by immunohistochemistry analysis, and the expressions of IL-1β, IL-6, and MCP-1 mRNA were measured by qRT-PCR. The results showed that CMP suppressed the expressions of CD68, IL-1β, IL-6, and MCP-1 mRNA induced by STZ. The role of autophagy in the treatment of DN mice with CMP was detected by TEM and western blotting. The results showed that the administration of CMP was able to overcome the STZ-treated autophagy deficiency, significantly increase the rate of autophagy in the kidney, promote the expression of Atg5, beclin1 and LC3 protein, and reduce the expression of p62 protein. In conclusion, the present study demonstrates that CMP exert a protective effect on DN in STZ-treated mice possibly via activation of autophagy.
本研究旨在探讨蛹虫草多糖（CMP）对链脲佐菌素（STZ）诱导的糖尿病肾病（DN）小鼠的保护作用。采用傅里叶变换红外光谱（FT-IR）和高效液相色谱（HPLC）对 CMP 进行鉴定。雄性 C57BL/6 小鼠连续 5 天腹腔注射柠檬酸缓冲液中的链脲佐菌素（STZ，50mg/kg）诱导糖尿病肾病。在 STZ 处理的小鼠中，给予 200 和 400mg/kg 的 CMP 或 60mg/kg 的厄贝沙坦可以预防 STZ 引起的损伤。CMP 显著降低了 STZ 诱导的肾脏指数、TC、TG、MDA、尿蛋白、Scr 和 BUN 的升高，同时显著增加了 GSH 水平的降低，与 DN 组相比。PAS、Masson 和 HE 染色的肾脏组织病理学分析证实了 STZ 诱导的肾脏损伤和 CMP 的保护作用。透射电子显微镜（TEM）结果证实了 STZ 诱导的足突融合严重，但 CMP 治疗抑制了足细胞的结构缺陷，并改善了足细胞的功能。免疫荧光法测量了 desmin 的表达，与 podocyte 损伤有关。结果表明，CMP 减轻了 STZ 诱导的 desmin 表达。通过免疫组化分析测量了 CD68 的表达，通过 qRT-PCR 测量了 IL-1β、IL-6 和 MCP-1 mRNA 的表达。结果表明，CMP 抑制了 STZ 诱导的 CD68、IL-1β、IL-6 和 MCP-1 mRNA 的表达。通过 TEM 和 Western blot 检测 CMP 治疗 DN 小鼠时自噬的作用。结果表明，CMP 给药能够克服 STZ 处理的自噬缺陷，显著增加肾脏中的自噬率，促进 Atg5、beclin1 和 LC3 蛋白的表达，并降低 p62 蛋白的表达。总之，本研究表明 CMP 通过激活自噬对 STZ 诱导的糖尿病肾病小鼠发挥保护作用。
